CADPE inhibits PMA-stimulated gastric carcinoma cell invasion and matrix metalloproteinase-9 expression by FAK/MEK/ERK-mediated AP-1 activation.

Metastasis is one of the main causes of death for patients with malignant tumors. Aberrant expression of matrix metalloproteinase-9 (MMP-9) has been implicated in the invasion and metastasis of various cancer cells. Here, we found that caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) could inhibit the migration and invasion of human gastric carcinoma cells in Transwell migration assays. To understand the underlying mechanism, we showed that CADPE significantly inhibited phorbol 12-myristate 13-acetate (PMA)-induced increases in MMP-9 expression and activity in a dose-dependent manner. The inhibitory effect of CADPE on MMP-9 expression correlated well with the suppression of MMP-9 promoter activity and the reduction of MMP-9 mRNA. Reporter gene assay and electrophoretic mobility shift assay showed that CADPE inhibited MMP-9 expression by suppressing the activation of the nuclear transcription factor activator protein-1 (AP-1) and c-Fos, but not NF-κB. Moreover, CADPE inhibited PMA-induced phosphorylation of protein kinases involved in AP-1 activation, such as focal adhesion kinase (FAK), mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK), and ERK1/2, whereas CADPE had little effect on the phosphorylation of p38 and c-jun NH(2)-terminal kinase. Taken together, our findings indicate that CADPE could be a unique antitumor agent that specifically inhibits MMP-9 activity by targeting the activation of FAK/MEK/ERK protein kinases and AP-1 transcription factor.

Han H ，Du B ，Pan X ，Liu J ，Zhao Q ，Lian X ，Qian M ，Liu M ... -  《-》

Hyul-Tong-Ryung suppresses PMA-induced MMP-9 expression by inhibiting AP-1-mediated gene expression via ERK 1/2 signaling pathway in MCF-7 human breast cancer cells.

Kim KS ，Yao L ，Lee YC ，Chung E ，Kim KM ，Kwak YJ ，Kim SJ ，Cui Z ，Lee JH ... -  《-》

Kalopanaxsaponin A inhibits PMA-induced invasion by reducing matrix metalloproteinase-9 via PI3K/Akt- and PKCdelta-mediated signaling in MCF-7 human breast cancer cells.

Park SK ，Hwang YS ，Park KK ，Park HJ ，Seo JY ，Chung WY ... -  《-》

EGCG blocks tumor promoter-induced MMP-9 expression via suppression of MAPK and AP-1 activation in human gastric AGS cells.

Kim HS ，Kim MH ，Jeong M ，Hwang YS ，Lim SH ，Shin BA ，Ahn BW ，Jung YD ... -  《ANTICANCER RESEARCH》

Ascofuranone suppresses PMA-mediated matrix metalloproteinase-9 gene activation through the Ras/Raf/MEK/ERK- and Ap1-dependent mechanisms.

Cho HJ ，Kang JH ，Kwak JY ，Lee TS ，Lee IS ，Park NG ，Nakajima H ，Magae J ，Chang YC ... -  《CARCINOGENESIS》